Circadian rhythms show considerable plasticity: they synchronize to environmental light cycles, shift phase in response to single light pulses, and alter their free-running periods and their sensitivity to fight as a function of their light exposure history. The mechanisms underlying much of this plasticity are incompletely understood. We propose to investigate two instances of plasticity at the cellular level: one in the pineal and the other in the suprachiasmatic nucleus (SCN). We have discovered that mammalian pineal gland, although not normally photosensitive, may become photosensitive when cultured. Our first aim is to describe the changes produced by culturing the gland, define the optimal culture conditions for producing them and to test the hypothesis that these changes do not occur in vivo because they are suppressed by endogenous norepinephrine from sympathetic input to the developing pineal. We have recently observed dramatic changes in the distribution of cell bodies visualized with antisera to serotonin (5HT) as a consequence of light exposure history. Such cell bodies, which are normally found only in the raphe nuclei, appear in large numbers in the SCN of hamsters that have been held for 16-20 weeks in constant darkness. Our second aim is to explore this observation further by testing two hypotheses: 1) that the effect is caused either by the complete absence of light or by the absence of a daily environmental entraining signal; 2) that the 5HT in SCN cells is a consequence of changes in the uptake mechanism. If we are able to block 5HT uptake and eliminate the 5HT cell bodies in the SCN we will assess the effects of such blocking treatments on circadian physiology and behavior. Because the pineal and the SCN are both centrally important components of the mammalian circadian axis, changes in their morphology (and physiology) produced by the environment may well be involved in circadian behavioral plasticity. Light 5HT and circadian rhythmicity have all been shown to be important mediators of mental state. Our findings are most likely to relate to the biological basis of mood disorders. The collaborative work described in this proposal will extend and deepen the ties that already exist between the Neuroscience Institute at Morehouse School of Medicine and the neuroscience community at University of Virginia and will provide the principal investigator with opportunities for continued training and development.